Definition: relating to, or characterized by an increased osmotic pressure. Source: Modified by Maria Victoria Gonzaga
What is hyperosmotic? The word hyperosmotic is derived from two Greek words: ‘hyper’, meaning “excess” and ‘osmos‘, meaning “thrust” or “push”. So, what does hyperosmotic mean? Hyperosmotic describes a solution that exerts higher thrust or pushes through a membrane.
To have a clear understanding of this definition, we first need to understand that a solution is prepared by mixing two components, i.e. a solute and a solvent. For example: in an aqueous sugar solution, sugar is the solute and water is the solvent.
The amount of solute in a solution eventually determines the direction of the movement of the solvent in any system. It is a well-established fact that the difference in concentration results in the development of a concentration gradient that drives the movement of the molecules from a higher concentration towards a lower concentration. When the movement of the solvent (water) molecule occurs due to a concentration gradient across a semi-permeable membrane, then this process is known as osmosis.
Thus, a solution containing a higher amount of solute in comparison to a similar solution is known as a hyperosmotic solution. For example, seawater is hyperosmotic in comparison to freshwater or tap water. Thus, a cell from freshwater when placed in a beaker containing seawater will be exposed to a hyperosmotic environment.
The number of solute molecules per solution volume or weight is known as osmolarity. This osmolarity regulates the osmotic pressure exerted by a solution. This is especially important for the biological system wherein two solutions are separated by a membrane, which is usually semi-permeable in nature. Thus, the movement of molecules in a biological system across a biological membrane may be determined by osmolarity. The movement of molecules across the biological membrane is essential for maintaining cellular homeostasis. Therefore, osmolarity plays a role in maintaining cellular homeostasis.
The osmolarity of the human serum is tightly controlled within the range of 285–295 mOsm/kg. The majority of the human body cells have similar osmolarity and are said to be isotonic. The fluid having higher or lower osmolarity than the human serum is classified as hypertonic or hypotonic, respectively.
The difference in osmolarity results in the development of osmotic pressure, which eventually results in the generation of osmotic stress in a biological system. Osmotic pressure is the pressure or thrust applied to the solvent molecules to prevent them from moving through the membrane.
At this stage, it is very important to understand that tonicity and osmolarity are two different things and should not be considered synonyms. An isotonic solution is not necessarily isosmotic or vice versa. Similarly, a hyperosmotic solution is not necessarily a hypertonic solution. To understand this, we need to clearly understand the concept of tonicity.
Tonicity is the property of the non-penetrating solutes only and is always dependent on the comparing solution. Thus, for a mammalian cell, an isosmotic sucrose solution will be isotonic but for a plant cell, an isosmotic sucrose solution would be hypotonic. This is because sucrose cannot permeate in a mammalian cell due to a lack of transporters in it while sucrose can permeate in a plant cell due to the presence of transporters. Thus, the non-permeability of sucrose in the mammalian cell will result in the isotonicity of isosmotic sucrose solution in mammalian cells.
In view of this, an important question thus arises. How can a solution be hyperosmotic and hypotonic?
To understand this, it is important to keep in mind that tonicity is determined only by the non-penetrating solutes. So, if a solution has a lower concentration of non-penetrating solutes, it would be referred to as hypotonic. A classical example of a hypotonic solution is a 5% dextrose solution having no non-penetrating solutes. When a cell is placed in a hyperosmotic but hypotonic solution like 10% dextran, water movement will occur. Therefore, a solution can be hyperosmotic and hypotonic.
In biology, when the osmolarity of the extracellular fluid is greater than the intracellular fluid, then the cell is referred to as exposed to a hyperosmotic environment and will experience hyperosmotic stress.
A higher osmolarity of the extracellular fluid results in the water flux out of the cell that results in the cell shrinkage, and eventually dehydration of the cell. (Figure 1).
So, what happens to a cell in a hyperosmotic solution? Exposure of a cell to a hyperosmotic solution can be highly detrimental to it. Such cells will have to deal with water efflux, which eventually results in the disruption of various cellular processes, such as disruption of the synthesis and repair of DNA, protein translation and its degradation, and the malfunctioning of mitochondria. The hyperosmotic condition results in cell shrinkage and the convolution of the nucleus. The cell shrinkage eventually induces apoptosis leading to cell death.
Conversely when the osmolarity of the extracellular fluid is less than the intracellular fluid, then the cell is said to be exposed to a hypoosmotic environment. In such an environment influx of the water /solvent will occur (Figure 1).
Physiological Significance of the Hyperosmotic Property
The human body is highly adaptive to such changes and in order to do so, the cells undergo osmo-adaptive responses wherein the cells try to adapt to such environmental changes and restore homeostasis. However, failure to restore this homeostasis often results in a diseased or inflammatory condition in the body.
The imbalance in osmolarity can be detrimental to cells and biological processes and can result in a diseased state. This homeostasis of osmolarity in the human body is controlled tightly through the kidney along with the antidiuretic hormone, arginine vasopressin (AVP) released from the posterior pituitary. An increase in plasma osmolarity induces the release of AVP from the pituitary gland. AVP, then, acts on the kidney and increases the membrane permeability of the distal tubule in order to increase the tubular reabsorption of water from the kidney. The kidney regulates the proportion of the solute as well as water in the urine.
Depending on the body fluid condition, the urine output can have low osmolarity (50 mOsm/L) or high osmolarity (1200-1400 mOsm/L). The low osmolarity urine output occurs when the body has an excess of water and extracellular fluid has low osmolarity. In this condition the urine is hypoosmotic. On the contrary, when the body has a deficiency of water and extracellular fluid has high osmolarity, hyperosmotic urine formation occurs. Body fluids having higher osmolarity signals the pituitary to release the AVP, which thereby increases the tubular water reabsorption from the kidney. As a result, due to water reabsorption, the amount of water is reduced from the urine output resulting in the formation of highly concentrated urine or hyperosmotic urine.
Alteration in the osmolarity has also been found to be associated with the induction of inflammatory processes in the body. High extracellular fluid osmolarity has been found to be associated with diseases like hypernatremia, heat stroke, diabetes, tissue burns, dehydration, asthma, cystic fibrosis, and uremia. Pro-inflammatory cytokines such as TNF, IL1β, IL6, IL8, and IL18 have been found to be related to hyperosmotic stress-related pathologies.
For instance: In kidneys, the tubular fluid is:
- iso-osmotic (to plasma) when it is at the beginning of the loop of Henle
- hyperosmotic (to plasma) when it is at the tip of the loop
- hypo-osmotic (to plasma) when it leaves the loop
Therapeutic Applications of the Hyperosmotics
Hyperosmotic agents are used for the treatment of Glaucoma. Glaucoma is an eye or ophthalmic disorder wherein there is an increase in intraocular pressure (IOP). An increase in IOP is a highly painful condition for the patient along with poor visualization. Hyperosmotic agents diminish the IOP by generating an osmotic gradient between the blood and the intraocular fluid compartments which results in the flux of ophthalmic fluid to the blood. This therapeutic approach is preferred when the glaucoma is nonresponding to the carbonic anhydrase inhibitors administered topically or even systemically. However, hyperosmotic agents have a short duration of efficacy and also induce systemic side effects.
In glaucoma, IOP is elevated due to vitreous fluid in the eye. On administration of hyperosmotic agents, the osmolality of the intravascular fluid increases (hyperosmolarity). However, the ophthalmic barrier does not allow the permeation of these agents into the vitreous humor. This results in the generation of the osmotic gradient. This, in turn, results in the fluid from vitreous efflux into the vascular fluid. Consequently, the reduced amount of vitreous humor reduces the IOP in the patient.
Almost a 3-4% reduction in IOP has been reported on the administration of the hyperosmotic agents in patients with glaucoma. The efficacy of these agents depends on a number of factors like molecular weight, dose, concentration, rate of administration, mode of administration, excretion rate, distribution, and ophthalmic penetration.
Some of the examples of hyperosmotic used in glaucoma therapy are glycerin, urea, isosorbide, mannitol, etc. These agents can be given topically, parenterally as well as orally. However, systemic (parenteral) or oral administration of these agents might result in certain side effects (Table1).
|Table 1: Commonly used hyperosmotic agents for treating ocular disease, Glaucoma, and their dose and potential side effects|
|Hyperosmotic agent||Route of administration||Dose and duration of action||Side effects|
|Isosorbide||Oral||1.5-2.0 g/kg; 3.5-4.5h||Nausea, vomiting|
|Glycerin||Oral||1.0-1.5 g/kg; 4-5h||Hyperglycemia/glycosuria, high calorie, Nausea, vomiting, headache|
|Mannitol||I.V injection||10%-20% solution; up to 6h||Allergy, Pulmonary edema, heart failure|
|Urea||I.V injection||30% solution; up to 5-6h||Thrombophlebitis, Tissue necrosis, headache, nausea, vomiting, transient elevation in blood urea nitrogen|
Hyperosmotic agents are also used for improving visualization in patients with corneal edema wherein, hyperosmotic agents cause transient dehydration to relieve the oedematous condition of the cornea. Apart from corneal edema, hyperosmotic agents are also used in the management of cerebral edema. Hyperosmotic agents can also be potentially utilized in the treatment of hypovolemic hemorrhage, as a plasma volume expander. A mixture of 7.5% NaCl (sodium chloride) and 6% dextran-70, have been reported to be an effective plasma expander. This composition of hyperosmotic agents (NaCl and dextran) has also been reported to significantly reduce mortality due to traumatic hypotension and head injury. The treatment with the hyperosmotic agent has been reported to induce rapid cardiovascular effects, which include elevation in cardiac parameters like arterial pressure, cardiac output, the volume of plasma, cardiac contraction, mean circulatory systemic pressure, and oxygen delivery and its consumption.
Hyperosmotic Stress in Plants
Not only animals are prone to physiological disruptions due to hyperosmotic stress but also plants. Hyperosmotic stress in plants is often caused by hyperosmotic conditions (when the osmolarity outside is higher than the inside of the cell). The common causes are the high salt concentration of the soil or when there is drought. When this happens, the plants counter the efflux of water and the eventual decrease in cell volume by a change in the genetic expression, production of intracellular osmolytes, and active endocytosis as well as ion sequestration through vacuolar transport. Otherwise, the plant cell might die from loss of turgor pressure and the collapse of the plasma membrane when the extreme perturbation is not fixed soon.
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